title: HLA-C heavy chains free of beta2-microglobulin: distribution in normal tissues and neoplastic lesions of non-lymphoid origin and interferon-gamma responsiveness.
abstract: Lacking monospecific antibodies to HLA-C, the expression and synthesis of these molecules have been difficult to evaluate. Using biochemical and flow cytometry approaches, the present report demonstrates that the reactivity of the murine monoclonal antibody L31 is restricted to naturally occurring HLA-C (HLA-Cw1 through -Cw8), HLA-B8 and HLA-B51 heavy chains not associated with beta2-microglobin (beta2m). This is due to two properties of HLA-C heavy chains: (a) they share the L31 epitope which distinguishes them from all the HLA-A and most HLA-B molecules; (b) they accumulate intracellularly, in a beta2m-free form, in much greater amounts than most L31-reacting HLA-B heavy chains. On the basis of this restricted reactivity, a representative panel of normal and neoplastic human tissues and cells derived from HLA-B8- B51- individuals was selected and employed to assess the tissue distribution, surface expression and IFN-gamma responsiveness of beta2m-free HLA-C heavy chains. At variance from antibody W6/32 to beta2m-associated heavy chains, L31 stains normal and neoplastic tissues with a ground-glass pattern and weakly binds to the surface of viable cells, even after treatment with interferon gamma (IFN-gamma). Thus, beta2m-free HLA-C heavy chains are, for the most part, located intracellularly. In spite of their distinct cellular localization, L31- and W6/32-reacting molecules have an overlapping tissue distribution, undergo concordant changes upon transformation and are upregulated in their synthesis by IFN-gamma to a similar extent. These observations demonstrate a coordinate regulation of HLA-C with HLA-A and -B molecules. In addition, they indicate that the assembly of HLA-C is impaired in most body districts and IFN-gamma is unable to completely reverse this impairment. The present results are consistent with a low surface expression of HLA-C and with a privileged role of these molecules in signaling class I loss to cytotoxic effectors in pathological conditions.
authors.affiliation: Immunology Laboratory, Regina Elena Cancer Institute, Rome, Italy. giacomini@crs.ifo.it
authors.forename: P
authors.initials: P
authors.lastname: Giacomini
authors.forename: A
authors.initials: A
authors.lastname: Beretta
authors.forename: M R
authors.initials: MR
authors.lastname: Nicotra
authors.forename: G
authors.initials: G
authors.lastname: Ciccarelli
authors.forename: A
authors.initials: A
authors.lastname: Martayan
authors.forename: C
authors.initials: C
authors.lastname: Cerboni
authors.forename: L
authors.initials: L
authors.lastname: Lopalco
authors.forename: D
authors.initials: D
authors.lastname: Bini
authors.forename: L
authors.initials: L
authors.lastname: Delfino
authors.forename: G B
authors.initials: GB
authors.lastname: Ferrara
authors.forename: A G
authors.initials: AG
authors.lastname: Siccardi
authors.forename: P G
authors.initials: PG
authors.lastname: Natali
mesh_terms: D000328:Adult; D000818:Animals; D002461:Cell Line, Transformed; D005434:Flow Cytometry; D017353:Gene Deletion; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D059949:HLA-B51 Antigen; D015795:HLA-B8 Antigen / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology*; D019073:HT29 Cells; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D008221:Lymphoid Tissue; D051379:Mice; D009369:Neoplasms / Q000276:immunology; D011233:Precipitin Tests; D011994:Recombinant Proteins; D014018:Tissue Distribution; D016707:Tissue Fixation; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000276:immunology*
chemical_list: D015235:HLA-B Antigens; D059949:HLA-B51 Antigen; D015795:HLA-B8 Antigen; D015236:HLA-C Antigens; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D007371:Interferon-gamma